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2010 Grants - Krishnamurthy

Cellular Pathways for Antibody Mediated Removal of Tau Aggregates

Pavan Kumar Krishnamurthy, Ph.D.
New York University School of Medicine
New York, New York

2010 New Investigator Research Grant

Much Alzheimer research has focused on "vaccines" that use the body's own immune system to reduce beta-amyloid in the brain. Beta-amyloid is a protein fragment that forms the amyloid plaques characteristic of Alzheimer's disease. However, recent studies have found that a similar immunization method may target another key feature of Alzheimer's, abnormal tau protein. Accumulations of this protein form characteristic neurofibrillary tangles in the Alzheimer brain.

In preliminary research with mice engineered to develop tau-related pathologies, Pavan Kumar Krishnamurthy, Ph.D., and colleagues identified a tau-based vaccine that cleared accumulations of abnormal tau and slowed the development of neurofibrillary tangles. This treatment also reduced tau-related cognitive deficits in the mice. For their current proposal, the researchers plan to administer various tau antibodies in model brain slices from normal mice and from mice with established tau pathology. They will then assess the antibodies' effectiveness at clearing different forms of tau in the slices. They will also assess how the vaccines ameliorate molecular processes that lead to tau-related damage.

The results of this effort could reveal important information about the mechanisms underlying tau pathology. They could also provide the basis for a broad range of tau vaccine therapies.